CTNND2

protein-coding

catenin delta 2, the group of Armadillo repeat containing|p120 catenin family

Gene summary

This gene encodes an adhesive junction associated protein of the armadillo/beta-catenin superfamily and is implicated in brain and eye development and cancer formation. The protein encoded by this gene promotes the disruption of E-cadherin based adherens junction to favor cell spreading upon stimulation by hepatocyte growth factor. This gene is overexpressed in prostate adenocarcinomas and is associated with decreased expression of tumor suppressor E-cadherin in this tissue. This gene resides in a region of the short arm of chromosome 5 that is deleted in Cri du Chat syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2013]

MANE transcript

NM_001332.4

Inheritance

ClinVar variants

P:18U:191B:81

Top phenotype

complex neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr5:10,971,836-11,904,446

External References & Databases

Ensembl (ENSG00000169862)

Transcript & Mutation Effects

hg38 • Region Span ~932.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Illumina

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: G2P

benign adult familial myoclonic epilepsySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019448

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CTNND2 variants in ClinVar

9 Conditions Cataloged

not providedTotal: 169

Inborn genetic diseasesTotal: 166

not specifiedTotal: 56

CTNND2-related disorderTotal: 42

Neurodevelopmental disorderTotal: 3

Complex neurodevelopmental disorderTotal: 3

CTNND2-associated Neurodevelopmental syndromeTotal: 2

CTNND2-associated neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001332.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	47 clinvar	3 clinvar	51
missense		2 clinvar	181 clinvar	29 clinvar	2 clinvar	214
nonsense	2 clinvar	5 clinvar	3 clinvar			10
start loss						0
frameshift	4 clinvar	4 clinvar	4 clinvar			12
splice donor/acceptor (+/-2bp)		1 clinvar	2 clinvar			3
Total	6	12	191	76	5	290

Highest pathogenic variant AF is 6.84061e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001332.4	RefSeq	NP_001323.1	22	MANE Select
ENST00000304623.13	Ensembl	ENSP00000307134.8	22	MANE Select
NM_001288715.1	RefSeq	NP_001275644.1	20	Standard
NM_001288716.1	RefSeq	NP_001275645.1	18	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ctnnd2b	Danio rerio	Structure: post-vent region Quality: curved abnormal

Gene / Model

Organism

Observed Phenotype

ctnnd2b

Danio rerio

Structure: post-vent region

Quality: curved

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ectoderm Differentiation

Biological Process

cell-cell junction assembly
cell adhesion
signal transduction
Wnt signaling pathway
synapse organization

Molecular Function

protein binding
beta-catenin binding
cadherin binding

Cellular Component

nucleus
cytoplasm
plasma membrane
cell-cell junction
cell-cell adherens junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000304623
Coding exons: 22
Length: 932204
Individuals with no LoFs: 125745
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125748
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.77	489	695	0.704	0.0000418	7827
Missense (PolyPhen)		100	209.08	0.47829		2173
Synonymous	-1.27	334	306	1.09	0.0000204	2539
Loss of Function	7.21	2	64.4	0.0310	0.00000352	692

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has a critical role in neuronal development, particularly in the formation and/or maintenance of dendritic spines and synapses (PubMed:25807484). Involved in the regulation of Wnt signaling (PubMed:25807484). It probably acts on beta- catenin turnover, facilitating beta-catenin interaction with GSK3B, phosphorylation, ubiquitination and degradation (By similarity). Functions as a transcriptional activator when bound to ZBTB33 (By similarity). May be involved in neuronal cell adhesion and tissue morphogenesis and integrity by regulating adhesion molecules. {ECO:0000250|UniProtKB:O35927, ECO:0000269|PubMed:25807484, ECO:0000269|PubMed:9971746}.;
Disease: DISEASE: Note=Defects in CTNND2, including deleterious missense and copy number variants (CNVs) are involved in autism, a complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate mental retardation. {ECO:0000269|PubMed:25807484}.;

Recessive Scores

pRec: 0.0936

Intolerance Scores

LoFtool: 0.00475
RVIS EVS: -2.41
RVIS percentile EVS: 1.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.815

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium